Influence of Delta-Like 1 on chemotherapeutic sensitivity of small cell lung cancer

Huanxin Liu,Linlang Guo,Yan Zhang,Zuoping Huang

doi:10.3329/bjp.v8i2.14234

Huanxin Liu, Linlang Guo + Show 2 more

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https://doi.org/10.3329/bjp.v8i2.14234

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Abstract

Our study investigated the role of Delta-Like 1 (DLL1) in multi-drug resistance of small cell lung cancer. Differentially expressed genes were detected in resistant small cell lung cancer H69AR cells and sensitive small cell lung cancer H69 cells by microarray. DLL1 expression in H69 cells and H69AR cells was further confirmed by RT-PCR and Western blot assay. eGFP-RNA was employed to up-regulate DDL1 expressing in H69AR cells (H69AR-eGFP-DLL1) by transfection. These cells were treated with different chemothera-peutics (ADM, DDP, and VP-16). Cell viability was detected. Cell cycle and apoptosis rate were determined. The DLL1 expression was significantly decreased in H69AR cells when compared with H69 cells. Over-expression of DLL1 increased the sensitivity of H69AR cells to chemotherapy, which was characterized by increase in apoptosis and arrest in G0/G1 phase. Our results demonstrate that up-regulation of DLL1 expression in small cell lung cancer cells may increase their sensitivity to chemotherapeutic agents.

Highlights

Small cell lung cancer (SCLC) cells have rapid cell proliferation resulting in rapid disease progression
CKK8 assay showed H69AR cells presented with markedly reduced sensitivity to DDP, ADM and VP-16 when compared with H69 cells (Figure 3A, p= 0.009)
H69AR cells transfected with pIRES2-EGFP delta-like 1 (DLL1) displayed dramatically increased sensitivity to DDP, ADM and VP-16 when compared with untransfected H69AR cells and H69AR cells transfected with pIRES2-EGFP-NC (Figure 3B, p= 0.016)

Summary

Introduction

Small cell lung cancer (SCLC) cells have rapid cell proliferation resulting in rapid disease progression. Patients usually develop hematological and/or lymph vessel metastasis at initial diagnosis. SCLC is the most malignant lung cancer. 80% of patients with SCLC respond favorably to early chemotherapy and/or radiotherapy, recurrence or disease progression is still present soon after treatment. Especially multidrug resistance (MDR), has been a major cause of failure in chemotherapy of SCLC (Chute et al, 1999; Sandler, 2003). 80% of SCLC patients are sensitive to early chemotherapy, relapse is common due to drug resistance. Patients with focal SCLC have a 5-year survival rate of

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